Smith Steven J, Zhang Hongbing, Clermont Anne O, Powers Alvin C, Kaufman Dixon B, Purchio Anthony F, West David B
Xenogen Corporation, Alameda, CA 94117, USA.
Mol Imaging. 2006 Apr-Jun;5(2):65-75.
We generated a transgenic mouse model (RIP-luc) for the in vivo monitoring of pancreatic islet mass and function in response to metabolic disease. Using the rat insulin promoter fused to firefly luciferase, and noninvasive technology to detect luciferase activity, we tracked changes in reporter signal during metabolic disease states and correlated the changes in luciferase signal with metabolic status of the mouse. Transgene expression was found to be specific to the pancreatic islets in this transgenic model. Basal transgene expression was tracked in male and female mice fed either a chow or a high-fat diet and in response to treatment with streptozotocin. Pancreatic bioluminescent signal increased in mice fed a high-fat diet compared with chow-fed animals. In a model of chemically induced diabetes, the bioluminescent signal decreased in accordance with the onset of diabetes and reduction of islet beta-cell number. Preliminary studies using islets transplanted from this transgenic model suggest that in vivo image analysis can also be used to monitor transplanted islet viability and survival in the host. This transgenic model is a useful tool for in vivo studies of pancreatic beta-cells and as a donor for islet transplantation studies.
我们构建了一种转基因小鼠模型(RIP-luc),用于在体内监测胰岛质量以及其对代谢性疾病的功能反应。通过将大鼠胰岛素启动子与萤火虫荧光素酶融合,并采用非侵入性技术检测荧光素酶活性,我们追踪了代谢疾病状态下报告基因信号的变化,并将荧光素酶信号的变化与小鼠的代谢状态相关联。在该转基因模型中,发现转基因表达对胰岛具有特异性。在喂食普通饲料或高脂饲料的雄性和雌性小鼠中,以及在链脲佐菌素处理后,对基础转基因表达进行了追踪。与喂食普通饲料的动物相比,喂食高脂饲料的小鼠胰腺生物发光信号增强。在化学诱导糖尿病模型中,生物发光信号随着糖尿病的发生和胰岛β细胞数量的减少而降低。使用从该转基因模型移植的胰岛进行的初步研究表明,体内图像分析也可用于监测移植胰岛在宿主中的活力和存活情况。这种转基因模型是用于胰腺β细胞体内研究的有用工具,也是胰岛移植研究的供体来源。